In the last couple of years, a series of techniques were developed which permit preparation of nuclei having a magnetic moment such that the population of the individual nuclear spin states differs to some extent substantially from the equilibrium state produced by the Boltzmann distribution. The associated changed population difference can be converted in an NMR experiment into a considerable increase of the signal intensity by factors of up to several thousand (so-called hyperpolarization). Conventional methods to obtain such hyperpolarization are based e.g. on the hyperpolarization of inert gases mediated through optical transitions, polarization-mediated through electron spin transitions of suitable radicals (dynamic nuclear polarization=DNP), via chemical reactions with spin-ordered substances (para-hydrogen polarization=PHP) or also thermal polarization at extremely low temperatures in extremely high magnetic fields. Mainly the three last-mentioned methods are particularly promising since they allow for polarization of a large number of substances which are also of medical-biological relevance.
Due to the deviation of the population differences from the equilibrium state, the lifetime of the generated hyperpolarization is limited, the polarized spin system will relax to the thermal equilibrium with the relaxation constant T1. For this reason, substances having long T1 constants are preferably used for such experiments. Corresponding experiments were initially carried out using inert gases which are easy to polarize and comprise very long T1 times. For DNP and PHP hyperpolarization, substances with C13 marked nuclei have been mainly used recently at suitable binding locations, wherein the above-mentioned principles of hyperpolarization may also be applied to other nuclei.
To measure NMR signals of such substances, it must be observed that the once-prepared magnetization which is originally present as z-magnetization, must be transferred into transverse magnetization for signal read-out, and subsequently decays to the equilibrium state at the transverse relaxation time T2 which is generally much faster. Magnetization excited through a 90° pulse is therefore available only once for read-out, such that many conventional NMR spectroscopy or MR imaging measurement methods are not suitable for application with hyperpolarized substances. Consequently, so-called gradient echo sequences with small flip angles are used for imaging experiments with corresponding substances, wherein with each excitation only a very small part of the polarized magnetization is read-out. Modified steady state sequences have recently also been used, in particular for 13C polarized substances, which permit multiple read-outs of the hyperpolarization through spin-echo formation when large flip angles (180°) are used after an initial 90° pulse, thereby providing maximum signal yield.
A particularly interesting and promising field of application of hyperpolarization measurement is the observation of the metabolic conversion of polarized substances. One can show e.g. that after venous injection of pyruvate a metabolic conversion to lactate and alanine is produced. The local metabolic rate, a parameter which is very important in particular in the diagnosis of cancer, can be determined through measurement of the lactate signal.
A precondition of the measurement is thereby the separate measurement of the signals of lactate, alanine and pyruvate, wherein preferably images corresponding to the spatial distribution of the metabolites are generated. In accordance with prior art, the spatial distribution of metabolites can be represented using so-called chemical shift imaging (CSI) techniques. One problem of these techniques is, however, that they considerably increase the measuring time: To record an image without chemical-shift encoding of a matrix size of n1×n2 image elements (pixels), n2 recording steps are sufficient since the first dimension of an image can be recorded in one recording step when the signal is read-out using a local encoding gradient. For a CSI experiment with a recording of s1 points in the direction of the spectroscopic dimension, n2×s1 recording steps are required, wherein s1 is in general in the range 8<s1<128. The total number of recording steps thereby increases by a factor s1. In case the number of recording steps is limited due to the lifetime of the polarized spins, the spatial resolution is correspondingly reduced by a factor s1.
As an alternative to a CSI experiment, chemical shift selective imaging (CSSI) methods may be carried out, wherein the chemical shift is selected through corresponding chemical shift selective preparation either of the signal phase or of the signal amplitude, and the signals are subsequently recorded using conventional imaging sequences. The most frequently used CHESS imaging method is, however, not suited for the inventive object, since the signal of one of the concerned metabolites is thereby suppressed and only the second is read-out while mapping of the metabolic conversion always requires recording of both (or more) metabolites.